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https://www.readbyqxmd.com/read/28445950/the-discovery-of-a-novel-compound-with-potent-antitumor-activity-virtual-screening-synthesis-biological-evaluation-and-preliminary-mechanism-study
#1
Yuanyuan Jin, Linhu Li, Zhaoyong Yang, Mingliang Liu, Huiyuan Guo, Weiyi Shen
Farnesyltransferase has been regarded as a promising drug target against cancer as it is critical for membrane association of several signal transduction proteins. In this study, a novel farnesyltransferase inhibitor (IMB-1406) was identified through virtual screening. It exhibits stronger potency (IC50s: 6.92-8.99 μM) than Sunitinib against all of the tested cancer cell lines. Preliminary studies on mechanism reveal that IMB-1406 induces apoptosis in HepG2 cells by arresting the cell cycle at the S phase, altering anti- and pro-apoptotic proteins leading to mitochondrial dysfunction and activation of caspase-3...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445553/a-novel-rat-head-gaze-determination-system-based-on-optomotor-responses
#2
Mengbo You, Toshiyuki Yamane, Hiroshi Tomita, Eriko Sugano, Takuya Akashi
The optomotor response of animals is commonly used to measure their visual performance, e.g., rats of different genetically altered strains or various drug tests. With the presentation of stimuli using computer screens or projectors, the common idea focuses on measuring the eye movement or head and/or body movement to characterize changes of the head gaze. However, traditional methods rely on either the invasive fixation of animals, or the judgment of a human observer who reports the stimulus-tracking movements...
2017: PloS One
https://www.readbyqxmd.com/read/28445233/preclinical-models-for-translational-sarcoma-research
#3
Rainer Hamacher, Sebastian Bauer
PURPOSE OF REVIEW: Sarcoma is a basket term for mesenchymal tumors for which more than 75 genetically and histologically distinct subtypes are recognized. Therapeutic progress has largely been achieved with classical chemotherapeutic drugs that were tested in empirical clinical trials. However, outcome in metastatic patients remains poor and with few exceptions numerous trials have failed or only provided limited improvement in recent years. RECENT FINDINGS: Given the genomic heterogeneity, preclinical model systems will be indispensable to identify new molecular targets and to prioritize drugs and drug combinations...
April 25, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28443941/knowledge-attitudes-and-perceptions-regarding-lymphatic-filariasis-study-on-systematic-noncompliance-with-mass-drug-administration
#4
Silvia Cabral, Cristine Bonfim, Rosalira Oliveira, Paula Oliveira, Terezinha Guimarães, Eduardo Brandão, Ana Maria Aguiar-Santos, Zulma Medeiros
The aim of this study was to investigate the epidemiological characteristics, antigenic profile, perceptions, attitudes and practices of individuals who have been systematically non-compliant in mass drug administration (MDA) campaigns targeting lymphatic filariasis, in the municipality of Olinda, State of Pernambuco, Northeastern Brazil. A pretested questionnaire was used to obtain information on socioenvironmental demographics, perceptions of lymphatic filariasis and MDA, and reasons for systematic noncompliance with treatment...
April 20, 2017: Revista do Instituto de Medicina Tropical de São Paulo
https://www.readbyqxmd.com/read/28441975/seek-test-treat-substance-using-women-in-the-hiv-treatment-cascade-in-south-africa
#5
Wendee M Wechsberg, Charles van der Horst, Jacqueline Ndirangu, Irene A Doherty, Tracy Kline, Felicia A Browne, Jennifer M Belus, Robin Nance, William A Zule
BACKGROUND: Women in South Africa who use alcohol and other drugs face multiple barriers to HIV care. These barriers make it difficult for women to progress through each step in the HIV treatment cascade from diagnosis to treatment initiation and adherence. This paper examines correlates of HIV status, newly diagnosed HIV status, and use of antiretroviral therapy (ART). METHODS: Outreach workers recruited sexually active Black African women who used substances in Pretoria as part of a U...
April 26, 2017: Addiction Science & Clinical Practice
https://www.readbyqxmd.com/read/28441497/development-of-a-biorelevant-material-sparing-membrane-flux-test-for-rapid-screening-of-bioavailability-enhancing-drug-product-formulations
#6
Aaron M Stewart, Michael E Grass, Deanna M Mudie, Michael M Morgen, Dwayne T Friesen, David T Vodak
Bioavailability-enhancing formulations are often used to overcome challenges of poor gastrointestinal solubility for drug substances developed for oral administration. Conventional in vitro dissolution tests often do not properly compare such formulations due to the many different drug species that may exist in solution. To overcome these limitations, we have designed a practical in vitro membrane flux test, requiring minimal active pharmaceutical ingredient (API) and capable of rapidly screening many drug product intermediates...
April 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28439316/epigenetic-assays-for-chemical-biology-and-drug-discovery
#7
REVIEW
Sheraz Gul
The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including cardiovascular, neurological and metabolic disorders. Despite these advances, the approved treatments for cancer only extend progression-free survival for a relatively short time and being associated with significant side effects...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28438204/evidence-on-anti-malarial-and-diagnostic-markets-in-cambodia-to-guide-malaria-elimination-strategies-and-policies
#8
Sochea Phok, Dysoley Lek
BACKGROUND: Understanding Cambodia's anti-malarial and diagnostic landscape in 2015 is critical for informing and monitoring strategies and policies as Cambodia moves forward with national efforts to eliminate malaria. The aim of this paper is to present timely and key findings on the public and private sector anti-malarial and diagnostic landscape in Cambodia. This evidence can serve as a baseline benchmark for guiding implementation of national strategies as well as other regional initiatives to address malaria elimination activities...
April 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28438197/anti-malarial-landscape-in-myanmar-results-from-a-nationally-representative-survey-among-community-health-workers-and-the-private-sector-outlets-in-2015-2016
#9
Si Thu Thein, Hnin Su Su Khin, Aung Thi
BACKGROUND: In 2015/2016, an ACTwatch outlet survey was implemented to assess the anti-malarial and malaria testing landscape in Myanmar across four domains (Eastern, Central, Coastal, Western regions). Indicators provide an important benchmark to guide Myanmar's new National Strategic Plan to eliminate malaria by 2030. METHODS: This was a cross-sectional survey, which employed stratified cluster-random sampling across four regions in Myanmar. A census of community health workers (CHWs) and private outlets with potential to distribute malaria testing and/or treatment was conducted...
April 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28438145/insights-into-the-availability-and-distribution-of-oral-artemisinin-monotherapy-in-myanmar-evidence-from-a-nationally-representative-outlet-survey
#10
Si Thu Thein, Hnin Su Su Khin, Aung Thi
BACKGROUND: The containment of artemisinin resistance in Myanmar, historically an important probable origin and route of anti-malarial resistance to the India sub-continent and beyond, is crucial to global malaria control and elimination. This paper describes what is currently known about the sale and distribution of oral artemisinin monotherapy (AMT) across Myanmar, where this medicine is commonly found. METHODS: A nationally representative 2015 outlet survey was conducted in the private sector, and among community health workers across four geographical domains...
April 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28438108/17-aag-and-apoptosis-autophagy-and-mitophagy-in-canine-osteosarcoma-cell-lines
#11
M Massimini, C Palmieri, R De Maria, M Romanucci, D Malatesta, M De Martinis, L Maniscalco, A Ciccarelli, L Ginaldi, P Buracco, L Bongiovanni, L Della Salda
Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28437733/the-establishment-of-in%C3%A2-vitro-culture-and-drug-screening-systems-for-a-newly-isolated-strain-of-trypanosoma-equiperdum
#12
Keisuke Suganuma, Shino Yamasaki, Nthatisi Innocentia Molefe, Peter Simon Musinguzi, Batdorj Davaasuren, Ehab Mossaad, Sandagdorj Narantsatsral, Banzragch Battur, Badgar Battsetseg, Noboru Inoue
Dourine is caused by Trypanosoma equiperdum via coitus with an infected horse. Although dourine is distributed in Equidae worldwide and is listed as an internationally important animal disease by the World Organization for Animal Health (OIE), no effective treatment strategies have been established. In addition, there are no reports on drug discovery, because no drug screening system exists for this parasite. A new T. equiperdum strain was recently isolated from the genital organ of a stallion that showed typical symptoms of dourine...
April 13, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28437452/enhanced-antibacterial-metabolite-production-through-the-application-of-statistical-methodologies-by-a-streptomyces-nogalater-niist-a30-isolated-from-western-ghats-forest-soil
#13
Jubi Jacob, Reshma Uma Rajendran, Syama Hari Priya, Jayamurthy Purushothaman, Dileep Kumar Bhaskaran Nair Saraswathy Amma
Streptomyces strains isolated from Nelliyampathy forest soil of Western Ghats, Kerala, India were evaluated for their antibacterial efficacy against two indicator pathogenic bacteria (Escherichia coli and Staphylococcus aureus). Among 140 strains tested, sixteen recorded potent antibacterial properties and were further screened against eleven bacterial pathogens. A strain identified as Streptomyces nogalater and designated as NIIST A30 exhibited maximum inhibition against all the test pathogens. Among the eight fermentation media tested, inorganic salts starch broth recorded the best for antibacterial production...
2017: PloS One
https://www.readbyqxmd.com/read/28437056/psychotic-and-bipolar-disorders-schizophrenia
#14
Alaina L Edmunds
Schizophrenia is the most common psychotic illness, typically appearing between the late teenage years and the mid-30s. The first episode of psychosis may be preceded by a prodromal period. Schizophrenia symptoms fall into six common symptom clusters: delusions and hallucinations, disorganization of speech, cognitive dysfunction, negative symptoms, affective symptoms, and motor system abnormalities. The diagnosis is based on criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, including exclusion of other possible medical or psychiatric etiologies of psychosis...
April 2017: FP Essentials
https://www.readbyqxmd.com/read/28436563/an-in-vitro-system-for-measuring-genotoxicity-mediated-by-human-cyp3a4-in-saccharomyces-cerevisiae
#15
Michael Fasullo, Julian Freedland, Nicholas St John, Cinzia Cera, Patricia Egner, Matthew Hartog, Xinxin Ding
P450 activity is required to metabolically activate many chemical carcinogens, rendering them highly genotoxic. CYP3A4 is the most abundantly expressed P450 enzyme in the liver, accounting for most drug metabolism and constituting 50% of all hepatic P450 activity. CYP3A4 is also expressed in extrahepatic tissues, including the intestine. However, the role of CYP3A4 in activating chemical carcinogens into potent genotoxins is unclear. To facilitate efforts to determine whether CYP3A4, per se, can activate carcinogens into potent genotoxins, we expressed human CYP3A4 in the DNA-repair mutant (rad4 rad51) strain of budding yeast Saccharomyces cerevisiae and tested the novel, recombinant yeast strain for ability to report CYP3A4-mediated genotoxicity of a well-known genotoxin, aflatoxin B1 (AFB1 )...
April 24, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28434766/stereoselective-synthesis-of-enantiopure-n-substituted-pyrrolidin-2-5-dione-derivatives-by-1-3-dipolar-cycloaddition-and-assessment-of-their-in-vitro-antioxidant-and-antibacterial-activities
#16
Siwar Ghannay, Sana Bakari, Ameni Ghabi, Adel Kadri, Moncef Msaddek, Kaïss Aouadi
1,3-Dipolar cycloaddition between a chiral nitrone and N-substituted maleimides afforded unprecedented enantiopure spiro-fused heterocycles in good yields with a high enantio- and diastereoselectivity. The reaction was taking place on the less hindered face of the nitrone. The obtaining heterocycles were screened for their in vitro antioxidant properties and the results revealed that the potent antioxidant activity was generally recorded to compounds (3g) and (3e). The in vitro antibacterial activities of these two compounds were also investigated and the results demonstrated the strongest potential of compound (3g) against all the tested bacteria...
April 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28434203/topiramate-monotherapy-for-juvenile-myoclonic-epilepsy
#17
REVIEW
Jia Liu, Lu-Ning Wang, Yu-Ping Wang
BACKGROUND: Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME. This is an updated version of the original Cochrane Review published in Issue 12, 2015. OBJECTIVES: To evaluate the efficacy and tolerability of topiramate monotherapy in the treatment of JME...
April 23, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28432357/in-silico-drug-discovery-approach-targeting-receptor-tyrosine-kinase-like-orphan-receptor-1-for-cancer-treatment
#18
Onkar Nath, Archana Singh, Indrakant K Singh
Receptor tyrosine kinases (RTK) are important cell signaling molecules that influence many cellular processes. Receptor tyrosine kinase such as orphan receptor 1 (Ror1), a surface antigen, is a member of the RTK family of Ror, which plays a crucial role in cancers that have high-grade histology. As Ror1 has been implicated to be a potential target for cancer therapy, we selected this protein for further investigation. The secondary and tertiary structure of this protein was determined, which revealed that this protein contained three β-sheets, seven α-helices, and coils...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431292/cannabis-and-cue-induced-craving-in-cocaine-dependent-individuals-a-pilot-study
#19
K Giasson-Gariépy, S Potvin, M Ghabrash, J Bruneau, D Jutras-Aswad
BACKGROUND: Cannabis consumption is common among cocaine users; however, little is known about its effect on cocaine craving. The objective of this study was to assess whether cannabis co-use is associated with lower cue-induced cocaine craving in non-treatment-seeking cocaine-dependent individuals. METHODS: Data from twenty-eight cocaine-dependent men were analyzed in this pilot study. Cocaine-dependent subjects (n=12) were compared with cocaine-dependent subjects who also abused or were dependent on cannabis (n=16)...
March 30, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28431115/spatial-distribution-of-falciparum-malaria-infections-in-zanzibar-implications-for-focal-drug-administration-strategies-targeting-asymptomatic-parasite-carriers
#20
Anders Björkman, Jackie Cook, Hugh Sturrock, Mwinyi Msellem, Abdullah Ali, Weiping Xu, Fabrizio Molteni, Roly Gosling, Chris Drakeley, Andreas Mårtensson
Background.: Optimal use of mass/targeted screen-and-treat or mass or focal drug administration as malaria elimination strategies remains unclear. We therefore studied spatial distribution of Plasmodium falciparum infections to compare simulated effects of these strategies on reducing the parasite reservoir in a pre-elimination setting. Methods.: P. falciparum rapid diagnostic tests (RDTs) and molecular (polymerase chain reaction [PCR]) and serological (enzyme-linked immunosorbent assay) analyses were performed on finger-prick blood samples from a population-based survey in 3 adjacent communities...
May 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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